The objective of this study is to evaluate the bioequivalence of a tablet formulation versus a capsule formulation of ASP8273 following a single dose under fasted condition in subjects with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. The study will also evaluate the safety and tolerability of a tablet formulation as a single dose and a capsule formulation as a single and multiple dose of ASP8273 in subjects with NSCLC harboring EGFR mutations.
Study and subjects will be divided into two phases: a pharmacokinetic (PK) and a postpharmacokinetic phase. The pharmacokinetic phase will follow a randomized, 2 period, 2 sequence single dose crossover design. Each period will be 5 days in duration. Within the sequence, both an ASP8273 tablet and ASP8273 capsule will be administered under fasted condition. The postpharmacokinetic phase will consist of up to 1 cycle (28 days) of continuous once daily dosing in post PK phase with ASP8273 capsules. Dose modifications are allowed if necessary in post PK phase and they follow a step-wise dose reduction. Subject is able to re-escalate dose level if reaction is stable.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
3
Oral
Beverly Hills Cancer Center
Beverly Hills, California, United States
Renovatio Clinical
The Woodlands, Texas, United States
US Oncology - Virginia Cancer Specialists, P.C. (VCS)
Fairfax, Virginia, United States
Pharmacokinetics of ASP8273 in plasma: Cmax
Cmax: Maximum plasma concentration. Pharmacokinetic phase only
Time frame: Up to Day 5 in each period of Phase 1 (maximum of 10 days)
Pharmacokinetics of ASP8273 in plasma: AUCinf
AUCinf: Area under the concentration time curve extrapolated to time infinity. Pharmacokinetic phase only
Time frame: Up to Day 5 in each period of Phase 1 (maximum of 10 days)
Pharmacokinetics of ASP8273 in plasma: AUClast
AUClast: Area under the concentration time curve from time zero to the last quantifiable concentration. Pharmacokinetic phase only
Time frame: Up to Day 5 in each period of Phase 1 (maximum of 10 days)
Pharmacokinetics of ASP8273 in plasma: AUC72
AUC72: Area under the concentration time curve truncated at 72 hours. Pharmacokinetic phase only
Time frame: Up to Day 5 in each period of Phase 1 (maximum of 10 days)
Pharmacokinetics of ASP8273 in plasma: t1/2
t1/2: Terminal elimination half-life. Pharmacokinetic phase only
Time frame: Up to Day 5 in each period of Phase 1 (maximum of 10 days)
Pharmacokinetics of ASP8273 in plasma: tmax
tmax: The time of maximum concentration. Pharmacokinetic phase only
Time frame: Up to Day 5 in each period of Phase 1 (maximum of 10 days)
Pharmacokinetics of ASP8273 in plasma: tlast
tlast: The time of last observed concentration. Pharmacokinetic phase only
Time frame: Up to Day 5 in each period of Phase 1 (maximum of 10 days)
Pharmacokinetics of ASP8273 in plasma: CL/F
CL/F: Oral clearance. Pharmacokinetic phase only
Time frame: Up to Day 5 in each period of Phase 1 (maximum of 10 days)
Pharmacokinetics of ASP8273 in plasma: Vz/F
Vz/F: Apparent volume of distribution. Pharmacokinetic phase only
Time frame: Up to Day 5 in each period of Phase 1 (maximum of 10 days)
Safety and tolerability assessed by nature, frequency, and severity of adverse events (AES)
For both pharmacokinetic and postpharmacokinetic phases
Time frame: Up to day 30
Number of participants with vital sign abnormalities and/or adverse events related to treatment
Vital signs include systolic and blood diastolic pressure, temperature and pulse rate. For both pharmacokinetic and postpharmacokinetic phases
Time frame: Up to day 30
Number of participants with laboratory abnormalities and/or adverse events related to treatment
Laboratory values include biochemical, hematological, coagulation and urine analysis. For both pharmacokinetic and postpharmacokinetic phases
Time frame: Up to day 30
Safety assessed by routine 12-lead electrocardiograms (ECG)
Routine 12-lead ECGs will be performed after the subject has been in a supine position for at least 5 minutes. For both pharmacokinetic and postpharmacokinetic phases
Time frame: Up to day 30
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